Acamprosate Suppresses Ethanol-Induced Place Preference in Mice With Ethanol Physical Dependence

Journal of Pharmacological Sciences

Masaya Higashioka²  Koji Mizuno¹  Michiko Oka²  Kazuhiro Kurokawa¹  Masaaki Hirouchi²  Masahiro Shibasaki¹  Seitaro Ohkuma¹ 

[1] Department of Pharmacology, Kawasaki Medical School, Japan;Research Laboratories, Nippon Shinyaku Co., Ltd., Japan

关键词: ethanol;    acamprosate;    alcohol dependence;    phospho-cAMP response element binding protein (p-CREB);    conditioned place preference;   

DOI  :  10.1254/jphs.13056FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(44)Cited-By(5)The present study investigated the effect of acamprosate on ethanol (EtOH)-induced place preference in mice with EtOH physical dependence. The expression of EtOH (2 g/kg, intraperitoneally)-induced place preference in mice without EtOH treatment before the experiment was dose-dependently suppressed by acamprosate. The levels of protein kinase A (PKA) and phospho-cAMP response element binding protein (p-CREB) in the limbic forebrain after EtOH-conditioning in naïve mice was unchanged. Furthermore, mice on the 4th day of withdrawal from continuous EtOH vapor inhalation for 9 days showed transient and significant enhancement of EtOH (1 g/kg, intraperitoneally)-induced place preference, which was significantly suppressed by acamprosate (300 mg/kg, oral administration; p.o., once a day) administered daily for 3 days after withdrawal from EtOH inhalation and during EtOH-conditioning. PKA and p-CREB proteins in the limbic forebrain of EtOH-conditioned mice on 4th day of withdrawal from continuous EtOH inhalation for 9 days significantly increased, which were completely abolished by acamprosate. These findings suggest that the signal transduction pathway via the PKA–p-CREB pathway in the limbic forebrain may be functionally related to the development of sensitization of EtOH-induced place preference and provide a possible molecular basis for the pharmacological effect of acamprosate to prevent or reduce the relapse of alcohol dependence.

【 授权许可】

Unknown